To better understand the mechanism of the anti-lipolytic effect of the sulfonylureas we have studied the effect of tolbutamide on cyclic AMP concentration and ATP concentration in isolated fat cells obtained from fat pads of rats. We have found that tolbutamide increases the concentration of cyclic AMP and at the same time is anti-lipolytic. We have also found that it decreases the concentration of ATP. We have also found that phenformin is anti-lipolytic and also increases the intracellular concentration of cyclic AMP. We plan to do further studies with tolbutamide and phenformin to clarify this paradoxical finding. We plan to study the effects of both tolbutamide and phenformin on respiration and oxidative phosphorylation in intact fat cells. We have also demonstrated that sodium salicylate inhibits lipolysi and appears to decrease the intracellular concentration of cyclic AMP and ATP. This apparent inhibition of cyclic AMP concentration may be the mechanism by which sodium salicylate inhibits lipolysis. We have studied lipolysis in human adipose tissue and have found that human adipose tissue does not respond to some lipolytic agents. To better understand the differences between lipolysis in human adipose tissue and rat adipose tissue we will study the effects of various lipolytic and anti-lipolytic agents on the concentration of cyclic AMP in adipose tissue otained from humans undergoing laparotomy for other reasons. We will also study the adipose tissue from a strain of mice that have spontaneous diabetes. Adipose tissue from these mice may have decreased adenyl cyclase activity. We will study the rate of lipolysis in the fat cells from these diabetic mice. We wll also study the effects of anti-lipolytic agents on these fat cells. We will attempt to correlate the lipolysis and anti-lipolysis to the intracellular concentration of cyclic AMP in the fat cells prepared from these diabetic animals in an attempt to understand the different lipolytic and anti-lipolytic mechanisms in the adipose tissue from the diabetic animals. We are also studying the effects of tolbutamide and phenformin on cardiac muscle. We have found that tolbutamide increases contractility in the isolated beating rat heart does not increase the concentration of cyclic AMP in cardiac muscle.